Related Experiment Video
Updated: Aug 5, 2026
Multiplex Immunofluorescence Combined with Spatial Image Analysis for the Clinical and Biological Assessment of the Tumor Microenvironment
Published on: June 2, 2023
Profiling Dectin-2-Positive Tumor-Associated Macrophages Across Human Cancers by Immunohistochemistry
Jason Ptacek1, Tracey Lin1, Bharathi Vennapusa1
1Bolt Biotherapeutics, Redwood City, CA, USA.
Purpose:
To characterize the prevalence and distribution of Dectin-2-positive macrophages across human tumors and develop a research immunohistochemistry (IHC) assay to assess Dectin-2 in cancer tissues.
Materials And Methods:
CLEC6A, the gene encoding Dectin-2, was evaluated across 38 tumor types using The Cancer Genome Atlas (TCGA). A fit-for-purpose Dectin-2 IHC assay was developed using a monoclonal antibody selected from screening 11 anti-Dectin-2 antibodies. Assay performance was supported by Dectin-2-expressing and parental cell line controls, macrophage-associated staining patterns, and comparison with an orthogonal CLEC6A in situ hybridization method using RNAscope. Dectin-2 expression was assessed in tissue microarrays (TMAs; n=553 samples) across six cancer types and whole tissue sections (WTSs; n=137) across seven cancer types.
Results:
TCGA analysis identified enriched CLEC6A expression in several tumor types, including non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), and subsets of head and neck cancer (HNC) and colorectal cancer (CRC). By IHC, Dectin-2-positive macrophages were detected across tumor types, with notable heterogeneity within and across cancer types. In TMAs, NSCLC showed the highest frequency of Dectin-2-positive macrophage infiltration, with 38% of cases with staining ≥1% of tumor area, WTS analysis confirmed and expanded these findings, with ≥50% of NSCLC, melanoma, HNC, TNBC, and CRC samples showing Dectin-2-positive macrophages in ≥1% tumor area.
Conclusions:
Dectin-2 expression was observed in subsets of tumor-associated macrophages across multiple human cancers, with relatively enriched expression in NSCLC, melanoma, HNC, TNBC, and CRC. To our knowledge, this study represents the first broad protein-level characterization of Dectin-2 across multiple human tumor types, identifies cancers with relatively enriched Dectin-2-positive macrophage infiltration, and provides a foundation for future translational studies of Dectin-2-targeted therapies.
